Radiolabeled Compound Producing Method and Producing Apparatus, Radiolabeled Compound and Radioisotope Producing Apparatus

ABSTRACT

The problem to be solved by the present invention is to provide a technique that allows producing a novel radiolabeled compound. The invention is a method for producing a radiolabeled compound, the method including the steps of: irradiating an alloy of a target substance with a radiation beam, to generate two or more radioisotopes from the alloy, and allowing the two or more radioisotopes to migrate into a gas; a step of generating an intermediate label by allowing a first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; and a step of generating a final label by allowing a second radioisotope different from the first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with the intermediate label.

TECHNICAL FIELD

The present invention relates to a radiolabeled compound producingmethod and producing apparatus, a radiolabeled compound and aradioisotope producing apparatus.

BACKGROUND ART

In recent years, RI (radioisotope) drugs have come to be actively usedin the medical field, for instance in the treatment of cancer (see forexample PTL 1 and NPL 1 to 3).

CITATION LIST Patent Literature

-   [PTL 1] Japanese Patent Application Publication No. 2015-147767

Non Patent Literature

-   [NPL 1] T G Turkington, et al., “Measuring astatine-211    distributions with SPECT”, Phys. Med. Biol., 1993, 38, 1121-1130-   [NPL 2] Yuto Nagao, et al., “Astatine-211 imaging by a Compton    camera for targeted radiotherapy”, Applied Radiation and Isotopes,    2018, 139, 238-243-   [NPL 3] D. Scott Wilbur, et al., “Reagents for Astatination of    Biomolecules. 2. Conjugation of Anionic Boron Cage Pendant Groups to    a Protein Provides a Method for Direct Labeling that is Stable to in    Vivo Deastatination”, Bioconjugate Chem. 2007, 18, 1226-1240

SUMMARY OF INVENTION Technical Problem

For instance in RI therapeutic drugs administered for the purpose oftreating cancer radiation emitted towards the exterior the body is veryweak, and accordingly it is difficult to image the biodistribution ofthe RI therapeutic drugs through capture of radiation from outside thebody. Therefore, means that have been tried to date for accuratelygrasping drug accumulation at a lesion site, so as to perform anappropriate treatment, include a first means, namely imaging ofdistribution upon administration of an RI drug for imaging, and a secondmeans, namely imaging by capturing extremely weak radiation emitted fromthe RI therapeutic drug to the exterior of the body, using ahigh-sensitivity apparatus. In the first means, however, thebiodistribution of the RI drug may vary when the radioisotope bound to acarrier varies, even for a same carrier; accordingly, distributionimages obtained through administration of an RI drug for imaging are notnecessarily identical to those of the distribution in the case ofadministration of an RI drug for treatment. In the second means, theability of an apparatus for capturing and imaging, with highsensitivity, extremely weak radiation emitted from the RI therapeuticdrug to the exterior of the body is not sufficient, and it thusdifficult to obtain images of sufficiently high resolution.

Therefore, it is an object of the present invention to provide atechnique that allows producing a novel radiolabeled compound.

Solution to Problem

In order to solve the above problem, the present invention strives tomake it possible to produce a radiolabeled compound in which two or moreradioisotopes are bound to a single carrier, through the use of two ormore radioisotopes that are generated from an alloy of a targetsubstance, by irradiating the alloy as a target substance with aradiation beam, and thereupon allowing the radioisotopes to migrate intoa gas.

In further detail, the present invention is a method for producing aradiolabeled compound, the method including the steps of: irradiating analloy as a target substance with a radiation beam, to generate two ormore radioisotopes from the alloy, and allowing the two or moreradioisotopes to migrate into a gas; generating an intermediate label byallowing a first radioisotope, from among the two or more radioisotopeshaving migrated into the gas, to react with a label precursor; andgenerating a final label by allowing a second radioisotope differentfrom the first radioisotope, from among the two or more radioisotopeshaving migrated into the gas, to react with the intermediate label.

In the above producing method, an alloy as a target substance isirradiated with a radiation beam, and accordingly it becomes possible togenerate two or more radioisotopes within a liquid target, and togenerate a radiolabeled compound that is labeled with the two or moreradioisotopes. In the above producing method, two or more radioisotopescan be generated simultaneously within a liquid target, throughirradiation of the alloy as the target substance with a radiation beam;as a result, for instance the generated radioisotopes can bind quicklyto a carrier, even in cases where the radioisotopes include aradioisotope of short half-life, and a radiolabeled compound can begenerated that is labeled with the two or more radioisotopes.

In the present invention, the method for producing a radiolabeledcompound may include the steps of: irradiating an alloy as a targetsubstance with a radiation beam, to generate two or more radioisotopesfrom the alloy, and allowing the two or more radioisotopes to migrateinto a gas; generating a first intermediate label by allowing a firstradioisotope, from among the two or more radioisotopes having migratedinto the gas, to react with a label precursor; generating a secondintermediate label by allowing a second radioisotope different from thefirst radioisotope, from among the two or more radioisotopes havingmigrated into the gas, to react with a label precursor; and generating afinal label by condensing the first intermediate label and the secondintermediate label. Such a producing method as well allows generating aradiolabeled compound that is labeled with two or more radioisotopes.

The above method for producing a radiolabeled compound may furtherinclude a step of adjusting the temperature of the alloy so as to be atemperature at which both the first radioisotope and the secondradioisotope evaporate, during irradiation with the radiation beam. Insuch a producing method at least two radioisotopes, namely a firstradioisotope and a second radioisotope from among the multipleradioisotopes generated in the alloy, migrate into a gas, as a result ofwhich the radioisotopes having migrated into the gas can be bound to acarrier.

The present invention can also be grasped from the aspect of a producingapparatus. For instance, the present invention may be an apparatus forproducing a radiolabeled compound, the apparatus having: isotopegeneration means for irradiating an alloy as a target substance with aradiation beam, to generate two or more radioisotopes from the alloy,and allowing the two or more radioisotopes to migrate into a gas; afirst generating unit which generates an intermediate label by allowinga first radioisotope, from among the two or more radioisotopes havingmigrated into the gas, to react with a label precursor; and a secondgenerating unit which generates a final label by allowing a secondradioisotope different from the first radioisotope, from among the twoor more radioisotopes having migrated into the gas, to react with theintermediate label.

The present invention may have for instance isotope generation means forirradiating an alloy as a target substance with a radiation beam, togenerate two or more radioisotopes from the alloy, and allowing the twoor more radioisotopes to migrate into a gas; a third generating unitwhich generates a first intermediate label by allowing a firstradioisotope, from among the two or more radioisotopes having migratedinto the gas, to react with a label precursor; a fourth generating unitwhich generates a second intermediate label by allowing a secondradioisotope different from the first radioisotope, from among the twoor more radioisotopes having migrated into the gas, to react with alabel precursor; and a fifth generating unit which generates a finallabel through condensation of the first intermediate label and thesecond intermediate label.

The present invention can also be grasped from the aspect of aradiolabeled compound. The present invention may be for instance aradiolabeled compound wherein two or more radioisotopes generated froman alloy of a target substance through irradiation of the alloy with aradiation beam, are bound to a single carrier.

The present invention may be a radiolabeled compound wherein astatine²¹¹At and iodine ¹²⁴I are bound to a single carrier.

The present invention can be grasped from the viewpoint of aradioisotope producing apparatus. For instance, the present inventionmay be an apparatus for producing a radioisotope, the apparatus having:a first container which stores a target substance; a second containerwhich receives a liquid transferred from the first container; a beamintroduction portion which is a passage of the radiation beam, forirradiating a target substance with a radiation beam within the firstcontainer; and an extraction unit which extracts, from a gas, aradioisotope generated in the first container by the radiation beam andwhich migrates into the gas in the second container, wherein the secondcontainer and the extraction unit are hermetically connected to eachother so that the gas that contains the radioisotope is conductedtherebetween.

Effects of Invention

The present invention allows producing a novel radiolabeled compound.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram illustrating an example of a radiolabeled compoundproducing apparatus.

FIG. 2 is a diagram illustrating an example of a radioisotope producingapparatus.

FIG. 3 is a diagram illustrating an example of a synthesis apparatus.

FIG. 4 is an example of a process flow performed in a radiolabeledcompound producing apparatus.

FIG. 5 is an image diagram illustrating cancer treatment and diagnosis.

FIG. 6 is a diagram illustrating a first variation of a radiolabeledcompound producing apparatus.

FIG. 7 is a diagram illustrating a variation of a radioisotope producingapparatus.

FIG. 8 is a diagram illustrating a second variation of a radiolabeledcompound producing apparatus.

FIG. 9 is a diagram illustrating a configuration example of aradioisotope producing apparatus of a second embodiment.

FIG. 10 is a diagram illustrating an example of the operation flow of aradioisotope producing apparatus.

FIG. 11 is a table illustrating examples of a relationship betweensaturated vapor pressure of elements in group 14, group 15, group 16 andgroup 17, and temperature.

FIG. 12 is a diagram illustrating a configuration example of aradioisotope producing apparatus in a variation of the secondembodiment.

DESCRIPTION OF EMBODIMENTS

Embodiments of the invention of the present application will beexplained next. The embodiments illustrated below are implementations ofthe present invention and are not meant to limit the technical scope ofthe invention of the present application.

First Embodiment

FIG. 1 is a diagram illustrating an example of a radiolabeled compoundproducing apparatus. The radiolabeled compound producing apparatus 1 isan apparatus in which an alloy as a target substance is irradiated witha radiation beam, to generate two or more radioisotopes, from the alloy,that are then allowed to migrate into a gas, whereupon the radioisotopesare combined with a label precursor. Accordingly, the radiolabeledcompound producing apparatus 1 is provided with a radioisotope producingapparatus 2 that generates radioisotope and causes the radioisotopes tomigrate into a gas, and a synthesis apparatus 3 which generates achimera RI molecule by allowing the radioisotopes to react with a labelprecursor. In the present application the term chimera RI denotes amolecule resulting from binding of two or more radioisotopes to onemolecule.

The term alloy denotes herein a mixture of two or more types of metals,the mixture being preferably at least solid or liquid at the temperatureof the space in which the radioisotope producing apparatus 2 isinstalled. The term label precursor denotes for instance a substance, inan RI therapeutic drug, to which the radioisotopes are bound, and thatis used as a carrier for transporting the radioisotope into the body.

FIG. 1 illustrates irradiation of an alloy of bismuth Bi and antimony Sbwith a radiation beam to generate, from the alloy, astatine ²¹¹At andiodine ¹²⁴I that are then allowed to migrate into a gas, whereupon theastatine ²¹¹At and the iodine ¹²⁴I are allowed to react with a labelprecursor, to thereby generate a final label in the form of a chimera RImolecule. In the radiolabeled compound producing apparatus 1 of thepresent embodiment, two or more radioisotopes are generatedsimultaneously in the radioisotope producing apparatus 2 by oneradiation beam, and the generated radioisotopes move at once into thesynthesis apparatus 3 and are allowed to react with a label precursor.Accordingly, the radiolabeled compound producing apparatus 1 is suitablefor synthesis of for instance a chimera RI molecule in which two or morehalogen-based radioisotopes such as astatine ²¹¹At and iodine ¹²⁴I areallowed to react with a label precursor. However, the radiolabeledcompound producing apparatus 1 is not limited to generating suchradiolabeled compounds.

FIG. 2 is a diagram illustrating an example of the radioisotopeproducing apparatus 2. The radioisotope producing apparatus 2 isprovided with a crucible 21 that holds an alloy of a target substance, aheater 22 that heats up the alloy in the crucible 21, a beam port 23 forprojecting a radiation beam to the alloy in the crucible 21, a gasintroduction port 24 for introducing gas into the crucible 21, and a gaslead-out port 25 for leading, out of the crucible 21, the gas that is tobe fed to the synthesis apparatus 3. Beam windows 26, 27 are provided inthe beam port 23. A jacket 28 is provided with the crucible 21.

The crucible 21 is a container for storing, in the interior thereof, atarget substance, and for melting at least part of thetarget-constituting substance. Preferably, the target substance ismelted into a liquid, in the crucible 21. Accordingly, the crucible 21is required to be at least heat-resistant enough to withstand atemperature of the melting point of the target substance. Therefore, forinstance quartz, ceramics, metals and the like are suitably used as thematerial of such a crucible 21. The crucible 21 is sealed, and openportions other than the gas introduction port 24 and the gas lead-outport 25 are closed, at the time of irradiating with the radiation beam.

The heater 22 is a heating means for heating the interior of thecrucible 21. The heater 22 heats up the interior of the crucible 21, tothereby heat up the target substance stored in the crucible 21. As aresult, melting of the target substance is promoted, and part or theentirety of the target substance can be melted and liquefied. Variousheating means, such as a micro sheath heater and others can be used assuch a heater 22. During irradiating with the radiation beam, theirradiated portion generates heat on account of the energy from theradiation beam, and hence heating by the heater 22 may be unnecessary insome instances.

The jacket 28 is a cooling space disposed around the crucible 21. Aninlet and an outlet of a coolant for cooling the crucible 21 areprovided with the jacket 28, such that the jacket 28 can be cooledthrough introduction of the coolant into the jacket 28 via the inlet.Also, natural heat dissipation elicited through discontinuation ofheating by the heater 22 can be expected to result in cooling of thecrucible 21. The crucible 21 can however be cooled more quickly throughintroduction of a coolant into the jacket 28. Examples of the coolantthat is introduced into the jacket 28 include for instance air in theroom in which the radiolabeled compound producing apparatus 1 isinstalled, or a gas such as nitrogen gas, or liquid such as water,prepared for the purpose of cooling of the crucible 21. The manner inwhich the crucible 21 is cooled may involve for instance allowing acoolant to flow thus in the jacket 28; or alternatively, providingcooling fins on the surface of the crucible 21, or providing athermoelectric conversion element such a Peltier element.

The beam port 23 is a tubular part running through a side wall portionof the crucible 21, and which forms a passage for allowing a radiationbeam, outputted from a radiation beam generator disposed in the vicinityof the crucible 21, to strike into the crucible 21. Accordingly, thetarget substance stored in the crucible 21 is disposed on an extensionline of the passage of the beam port 23. Both ends of the passage formedby the beam port 23 are closed by the beam windows 26, 27, in order toensure the sealability of the crucible 21. The beam windows 26, 27 arefor instance made up of a metal plate that lets radiation beams throughbut are not melted by the radiation beams. The interior of the beam port23 is evacuated or is filled with a gas (for instance He gas). Theradiation beam outputted from the radiation beam generator passesthrough the beam window 26, the interior of the beam port 23 and thebeam window 27 and reaches the target substance in the crucible 21.

The gas introduction port 24 is an inlet through which a gas isintroduced into the crucible 21. The gas lead-out port 25 is an outletfor discharging a gas from a gas phase portion of the crucible 21. Thegas introduction port 24 and the gas lead-out port 25 are for instancetubular pipes. The gas introduction port 24 allows a gas to flow intoand out the crucible 21. A gas for recovery of radioisotopes isintroduced through the gas introduction port 24. For instance, He gasthat is not radioactivated by radiation beams is suitably used as thegas that is introduced into the crucible 21. The gas is introducedthrough the gas introduction port 24, as a result of which the gas isdischarged from the gas lead-out port 25. In consequence, this elicitsflow of gas from the gas introduction port 24 towards the gas lead-outport 25, in the gas phase portion in the crucible 21. As a result ofsuch gas flow, it becomes possible to discharge, via the gas lead-outport 25, radioisotopes that are generated in the target substancethrough irradiation with a radiation beam and that migrate into the gasin the gas phase portion. The flow rate of the gas discharged out of thegas lead-out port 25 and pressure in the crucible 21 can be adjusted byadjusting the flow rate of the gas that is introduced into the crucible21 through the gas introduction port 24, and/or by adjusting the degreeof opening of a flow rate adjustment valve that is provided in thevicinity of the gas lead-out port 25.

FIG. 3 is a diagram illustrating an example of the synthesis apparatus3. The synthesis apparatus 3 has two columns for allowing radioisotopesto react with a label precursor, namely a first column 31 through whichthe gas discharged from the gas lead-out port 25 of the radioisotopeproducing apparatus 2 passes, and a second column 32 through which gashaving passed through the first column 31 passes. The first column 31selectively captures a first radioisotope from among the two or moreradioisotopes generated from the alloy of the target substance in thecrucible 21 of the radioisotope producing apparatus 2, to perform an RIlabeling reaction of allowing the first radioisotope to react with thelabel precursor. In the first column 31, therefore, the firstradioisotope from among the two or more radioisotopes contained in thegas discharged from the gas lead-out port 25 of the radioisotopeproducing apparatus 2 is used in an RI labeling reaction, while thesecond radioisotope passes as-is through the first column 31. At thisstage the label precursor having the first radioisotope bound thereto inthe first column 31 is one type of intermediate label, as referred to inthe present application, since this label precursor precedes binding ofthe second radioisotope in the second column 32. Specifically, the termintermediate label in the present application denotes a label havingbound thereto at least either one of the two or more radioisotopes thatare to be bound, at a time prior to completion of binding all of the twoor more radioisotopes.

In the second column 32 on the downstream side of the first column 31,the second radioisotope having passed through the first column 31 iscaptured; the second radioisotope is allowed to react with theintermediate label having been labeled in the first column 31, togenerate a final label as a result. Schemes conforming to the compoundto be synthesized are utilized in the first column 31 and the secondcolumn 32. For instance, a batch method is used in a case where reactiontime is long, whereas a flow method is used in a case where reactiontime is short.

A normally RI labeling reaction is carried out in the first column 31.In a case for instance where an RI labeling reaction by astatine ²¹¹Atis carried out in the first column 31, an electrophilic substitutionreaction, a nucleophilic substitution reaction, an electrophilicaddition reaction or a radical reaction may be resorted to as ahalogenation reaction that can be utilized in the first column 31. Inorder to bind a radioactive halogen such as astatine ²¹¹At to forinstance a peptide, which is a type of carrier, firstly a peptidecompound, synthesized on site or procured commercially, is prepared andis bound to a carrier within the first column 31, after which astatine²¹¹At is bound to the peptide, at an appropriate reaction temperatureand during an appropriate reaction time, while under the concomitant useof an appropriate amount of an oxidant and/or a solvent.

The first column 31 is made up of devices conforming to various labelingmethods. In an on-column labeling method, for instance, the first column31 is made up of a solid-phase column that holds a reaction solution,and tubing for allowing the label precursor to pass through thesolid-phase column.

In the second column 32 as well an RI labeling reaction is carried out.In the second column 32 the radioisotope having passed through the firstcolumn 31 is allowed to react with the intermediate label, having beenlabeled in the first column 31 and having been transferred from thefirst column 31 to the second column 32, so that a final label isgenerated as a result. In a case for instance where astatine ²¹¹At isbound to a peptide in the first column 31, as described above, thepeptide having astatine ²¹¹At bound thereto corresponds herein to theintermediate label. Also in the second column 32, a halogenationreaction such as an electrophilic substitution reaction, a nucleophilicsubstitution reaction, an electrophilic addition reaction or a radicalreaction can be utilized, similarly to the first column 31. However, theamount of the intermediate label having been labeled in the first column31 and supplied to the second column 32 is very small, at most ofseveral tens of pmol; accordingly, a very small space is formed in thesecond column 32, so as to enable a pico-scale RI labeling reaction tobe carried out. The intermediate label generated in the first column 31is transferred to the second column 32, together with the radioisotopethat passes through the first column 31, as a result of unbinding of theintermediate label from the carrier in the first column 31. The methodfor separating the intermediate label from the carrier in the firstcolumn 31 depends on the binding method, but may involve for instancenatural separation from the carrier accompanying binding to theradioisotope, or may be a method in which an eluent containing anadditive that unbinds the intermediate label from the carrier in thefirst column 31 is injected. The intermediate label transferred to thesecond column 32 is bound to a carrier of the second column, within avery small space; the radioisotope having passed through the firstcolumn 31 becomes then bound to the intermediate label that is in turnbound to the carrier of the second column. In a case for instance whereastatine ²¹¹At and iodine ¹²⁴I are fed from the radioisotope producingapparatus 2 to the synthesis apparatus 3 by a gas, as described above,then iodine ¹²⁴I having passed through the first column 31 becomes boundto the intermediate label in the second column 32.

Various automation techniques that allow for quick and efficientsynthesis are preferably utilized in the synthesis apparatus 3, in orderto enable efficient synthesis of a label having a short half-life, suchas astatine ²¹¹At, as described above.

FIG. 4 is an example of a process flow performed in the radiolabeledcompound producing apparatus 1. Hereafter, the process flow performed inthe radiolabeled compound producing apparatus 1 will be explained withreference to the flowchart of FIG. 4.

In the case of generation of a radiolabeled compound using theradiolabeled compound producing apparatus 1, a substance conforming tothe label type is placed with the crucible 21 of the radioisotopeproducing apparatus 2, and a gas is injected through the gasintroduction port 24 at an appropriate flow rate. The crucible 21 isheated through energization of the heater 22 (S101). The targetsubstance in the crucible 21 melts when reaching the melting point, andbecomes a liquid alloy of the target substance, in the crucible 21. Forinstance, alloys of bismuth Bi and antimony Sb have a melting point ofabout 271° C. to 631° C., depending on the alloy ratio; accordingly, theinterior of the crucible 21 is preferably brought to a temperature thatis at least higher than the melting points of bismuth Bi and antimonySb, in a case where these are placed in the crucible 21. The alloy ratiois established herein as appropriate taking into consideration forinstance the type and structure of the RI drug to be produced, theproportion in which radioactive compounds generated by the radioisotopeproducing apparatus 2 move into the synthesis apparatus 3, and labelingratios and reaction times in the first column 31 and the second column32.

Next, the interior of the crucible 21 is irradiated with a radiationbeam via the beam port 23 (S102). Examples of radiation beams thatirradiates the interior of the crucible 21 include a-beams (⁴He²⁺),³He²⁺, ¹H⁺, ²H⁺, ⁷Li³⁺ and the like. The radiation beams utilized are¹H⁺, ²H⁺, ⁴He²⁺, ³He²⁺ or ⁷Li³⁺ in a case where target-constitutingsubstance is an element of group 13, group 14, group 15 or group 16. Inconsequence, the main radioisotopes generated as a result of a nuclearreaction between the target-constituting substance and the radiationbeam are elements of group 15, group 16, group 17 and group 18. In acase where an alloy of bismuth Bi and antimony Sb are stored in thecrucible 21, irradiation with a-beams into the crucible 21 results ingeneration of astatine ²¹¹At and iodine ¹²⁴I as radioisotopes, sinceboth bismuth Bi and antimony Sb are group 15 elements.

When the interior of the crucible 21 is irradiated with a radiationbeam, at least two radioisotopes become generated in the liquid phaseportion of the crucible 21. The multiple radioisotopes generated in thecrucible 21 ordinarily have mutually different boiling points. Forinstance, astatine ²¹¹At has a boiling point of 337° C. at normalpressure (1 atmosphere). The boiling point at normal pressure of iodine¹²⁴I is however 184° C. In the radiolabeled compound producing apparatus1 a configuration is adopted wherein the multiple radioisotopesgenerated in the crucible 21 and having migrated from the liquid phaseportion into the gas in the gas phase portion are fed to the synthesisapparatus 3; accordingly, the multiple radioisotopes generated in thecrucible 21 must all evaporate in the crucible 21 and migrate from theliquid phase portion into the gas in the gas phase portion. In theradiolabeled compound producing apparatus 1 of the present embodiment,therefore, the temperature in the interior of the crucible 21 isadjusted, for instance by the heater 22, so as to be higher than theboiling point of at least the radioisotope of highest boiling point fromamong the multiple radioisotopes that are to be fed to the synthesisapparatus 3. The temperature in the interior of the 21 is adjusted forinstance to be 337° C. or higher, although depending on the pressure inthe crucible 21, in a case for instance where both astatine ²¹¹At andiodine ¹²⁴I are allowed to evaporate in the crucible 21 and migrate fromthe liquid phase portion into the gas in the gas phase portion. Theboiling point of bismuth Bi is 1564° C. and the boiling point ofantimony Sb is 1587° C. The boiling point of alloys of bismuth Bi andantimony Sb is about 1562° C. to 1650° C., depending on the alloy ratio;accordingly, a liquid alloy which is the target substance does notevaporate so long as the interior of the crucible 21 is kept at atemperature lower than that.

The radioisotopes that evaporate from in the crucible 21 and move fromthe liquid phase portion in the crucible 21 into the gas in the gasphase portion flow out of the crucible 21, and into the synthesisapparatus 3, together with He gas that flows from the gas introductionport 24, through the interior of the crucible 21, and towards the gaslead-out port 25. In the first column 31 of the synthesis apparatus 3the first radioisotope, from among the two or more radioisotopescontained in the He gas that flows from the radioisotope producingapparatus 2 towards the synthesis apparatus 3, becomes bound to a labelprecursor, to generate an intermediate label. In the second column 32 ofthe synthesis apparatus 3, the second radioisotope having passed throughthe first column 31, from among the two or more radioisotopes containedin the He gas that flows from the radioisotope producing apparatus 2towards the synthesis apparatus 3, becomes bound to the intermediatelabel, and a final label is generated thereupon.

In a case for instance where an alloy of bismuth Bi and antimony Sb isstored as a target substance in the crucible 21, and astatine ²¹¹At andiodine ¹²⁴I generated in the crucible 21 as a result of irradiation witha-beams flow from the radioisotope producing apparatus 2 into thesynthesis apparatus 3, then an intermediate label in which astatine²¹¹At is bound to a label precursor is generated in the first column 31,and a final label, in which iodine ¹²⁴I is further bound to theintermediate label, is generated in the second column 32.

In the radiolabeled compound producing apparatus 1 of the embodiments,thus, an alloy serves as the target substance, and accordingly two ormore types of objective radioisotopes can be generated simultaneouslywithin a liquid target, and a radiolabeled compound that is labeled withtwo or more radioisotopes can likewise be generated, through irradiationof the alloy as the target substance with a same radiation beam. Theradiolabeled compound thus labeled with two or more radioisotopes can beused for instance in the manner described below.

FIG. 5 is an image diagram illustrating cancer treatment and diagnosis.For instance, astatine ²¹¹At having received attention in recent yearsas an a ray emitting nuclide for cancer treatment emits herein a-raycapable of selectively destroying cancer cells alone, since the range ofastatine ²¹¹ At within the body is short. However, images of an RI drugtaken up by cancer cells are indistinct, and insufficient for clinicaluse, as depicted by the “image” in the comparative example section ofFIG. 5, due for instance to sensitivity and resolution problems thatarise when attempting to capture human biodistribution of an RI druglabeled with astatine Hi which has a short half-life of about 7.2 hours,by single photon emission computed tomography (SPECT) or using a Comptoncamera, both techniques being sensitive to X-rays and gamma raysradiated by astatine ²¹¹At. By contrast, iodine ¹²⁴I has a comparativelylong half-life of about 4.2 days, and accordingly the humanbiodistribution of an RI drug labeled with iodine ¹²⁴I can be capturedby a positron emission tomographic (PET) apparatus for positron emissiontomography, which is an imaging technique relying on positron detection;as depicted by the “image” in the working example section of FIG. 5; animage of an RI drug taken up by cancer cells is clearly reflected inthis case, and can be sufficiently used in a clinical setting.

For instance as reported by D. Scott Wilbur et al. in NPL 3 above, thebiodistribution of the RI drug having astatine ²¹¹At bound thereto arenot identical to the biodistribution of an RI drug having iodine ¹²⁴Ibound thereto, even for a same label precursor. In conventional art itis therefore necessary to address differences in the distribution ofboth drugs where laying out a cancer treatment plan. In this regard, theradiolabeled compound producing apparatus 1 of the above embodimentallows two radioisotopes, namely astatine ²¹¹At and iodine ¹²⁴I, to bebound to a single carrier, and accordingly allows finely imaging, bymeans of a PET apparatus, the distribution of an RI drug administeredfor the purpose of treating cancer. Herein a radiolabeled compound thatmay be grasped under the appellation of “chimera RI drug” can be used asan RI drug that fulfills two functions, namely a therapeutic functionand an imaging function, through binding of two radioisotopes, i.e.astatine ²¹¹At and iodine ¹²⁴I having different natures, to a singlecarrier, despite the fact the radiolabeled compound is labeled withastatine ²¹¹At having a comparatively short half-life. The feasibilityof using such a chimera RI drug derives from the fact that theradiolabeled compound is produced using the radiolabeled compoundproducing apparatus 1 of the above embodiment, which allows generatingsimultaneously two or more radioisotopes through irradiation of an alloyas a target substance with a radiation beam, and allows binding the twoor more radioisotopes to a label precursor in a short time. Such achimera RI drug cannot be produced, on account of time constraints, inconventional producing methods that involve, for instance, irradiating asolid target with a radiation beam, and extracting a radioisotope,generated within the solid target, for instance by dry distillation.

In the configuration of the radiolabeled compound producing apparatus 1of the above embodiment, the first column 31 and the second column 32 ofthe synthesis apparatus 3 are disposed in series, such that the gasdischarged from the gas lead-out port 25 of the radioisotope producingapparatus 2 follows a path leading through the first column 31, afterwhich the gas flows to the second column 32. However, the first column31 and the second column 32 in the radiolabeled compound producingapparatus 1 may be disposed in parallel.

FIG. 6 is a diagram illustrating a first variation of the radiolabeledcompound producing apparatus 1. In the radiolabeled compound producingapparatus 1 of the above embodiment, a configuration may be adoptedwherein the columns in which the radioisotopes become bound to the labelprecursor are provided as two columns in parallel, such that the gasdischarged from the gas lead-out port 25 of the radioisotope producingapparatus 2 flows in parallel in the two columns, as illustrated in FIG.6. In that case two or more radioisotopes generated from the alloy of atarget substance in the crucible 21 of the radioisotope producingapparatus 2 flows in the two columns in the synthesis apparatus 3.Therefore, in one of the two columns of the synthesis apparatus 3 in thecase of the present first variation an RI labeling reaction is carriedout in which a first radioisotope, from among the two or moreradioisotopes generated from the alloy of the target substance in thecrucible 21 of the radioisotope producing apparatus 2, is selectivelycaptured, and is allowed to react with a label precursor, to generate afirst intermediate label. In the other of the two columns of thesynthesis apparatus 3 an RI labeling reaction is carried out in which asecond radioisotope different from the first radioisotope, from amongthe two or more radioisotopes generated from the alloy of the type thetarget substance in the crucible 21 of the radioisotope producingapparatus 2 is selectively captured, and is allowed to react with thelabel precursor, to generate a second intermediate label. The firstintermediate label and the second intermediate label generated in therespective columns are then condensed, to generate a final label.

In a case for instance where an RI drug of astatine ²¹¹At and iodine¹²⁴I such as the one exemplified in the above embodiment is produced inaccordance with the present first variation, an RI labeling reaction ofallowing astatine ²¹¹At to react with a label precursor is performed inone of the two columns of the synthesis apparatus 3. An RI labelingreaction of allowing iodine ¹²⁴I to react with a label precursor iscarried out in the other of the two columns of the synthesis apparatus3. For instance, any one from among an electrophilic substitutionreaction, a nucleophilic substitution reaction, an electrophilicaddition reaction and a radical reaction can be resorted to in thecolumn where astatine ²¹¹At is allowed to react with the labelprecursor, but an electrophilic substitution reaction is most suitableherein. Meanwhile, for instance any one from among an electrophilicsubstitution reaction, a nucleophilic substitution reaction, anelectrophilic addition reaction, a nucleophilic addition reaction and aradical reaction may be resorted to in the column in which iodine ¹²⁴Iis allowed to react with a label precursor; preferred herein are howeveran electrophilic substitution reaction, a nucleophilic substitutionreaction and an electrophilic addition reaction, and a radical reactionas a next preferred reaction.

The intermediate label of astatine ²¹¹At and the intermediate label ofiodine ¹²⁴I respectively generated in the two columns of the synthesisapparatus 3 are debound from the carrier in each column, are retrieved,and are condensed in another column. In the column in which condensationis carried out, a very small space for pico-scale condensation isformed, similarly to the above-described second column 32, since theintermediate labels are condensed with each other in the pico-scale.Upon condensation of the intermediate label of astatine ²¹¹At and theintermediate label of iodine ¹²⁴I a final label becomes perfected in theform of a chimera RI drug in which two radioisotopes, namely astatine²¹¹At and iodine ¹²⁴I are bound to a single carrier.

In the present first variation as well, similarly to the aboveembodiment, two or more radioisotopes can be generated simultaneouslywithin a liquid target, and a radiolabeled compound that is labeled withthe two or more radioisotopes can be generated, through irradiation ofan alloy as the target substance with a radiation beam. Thus, aradiolabeled compound having been thus labeled with two or moreradioisotopes can be used as an RI drug that delivers both a therapeuticfunction and an imaging function, as described above.

In the above embodiment an implementation is adopted in which theradioisotopes generated in the liquid phase portion of the crucible 21flow into the synthesis apparatus 3 from the gas phase portion of thecrucible 21, but the radiolabeled compound producing apparatus 1 of theabove embodiment is not limited to such a configuration.

FIG. 7 is a diagram illustrating a variation of a radioisotope producingapparatus. In the present modification, constituent elements identicalto those in the above embodiment are denoted by the same referencenumerals, and a detailed description thereof will be omitted. Aradioisotope producing apparatus 2A according to the present variationhas a configuration wherein the crucible 21 according to the aboveembodiment is herein separated into a target container 21A and a storagecontainer 21B. Similarly to the crucible 21 according to the aboveembodiment, the target container 21A is provided with a heater 22A thatheats up an alloy within the target container 21A, a beam port 23 forirradiating an alloy within the target container 21A with a radiationbeam, and a gas introduction port 24A for introducing a gas into thecrucible 21. Beam windows 26, 27 are provided in the beam port 23. Ajacket 28 is provided in the target container 21A.

The target container 21A is a container for storing, in the interiorthereof, a target-constituting substance, and for melting at least partof the target substance. Similarly to the crucible 21, the targetcontainer 21A is heat-resistant so as to be capable of withstanding thetemperature of the melting point of target-constituting substance. Atransfer pipe 29 for transfer of a liquid alloy from the interior of thetarget container 21A towards the storage container 21B is connected tothe bottom of the target container 21A.

The storage container 21B is a storage container that receives theliquid alloy transferred from the target container 21A. Similarly to thetarget container 21A, the storage container 21B has heat resistance thatallows withstanding the temperature of the melting point of the liquidalloy transferred from the target container 21A. An opening at the endof a transfer pipe 29 is disposed in the vicinity of the bottom of thestorage container 21B, so that the liquid alloy flowing through thetransfer pipe 29 flows out into the storage container 21B at the liquidphase portion of the storage container 21B. The storage container 21B isprovided with a heater 22B for heating the alloy within the storagecontainer 21B, a gas introduction port 24B for feeding a gas into thegas phase portion of the storage container 21B, and a gas lead-out port25 for feeding gas from the gas phase portion of the storage container21B to the synthesis apparatus 3. The storage container 21B alsofunctions as a heating container for heating the liquid alloytransferred from the target container 21A.

The explanation in FIG. 7 deals with an example of a configurationwherein the gas lead-out port 25 that is connected to the synthesisapparatus 3 is not provided in the target container 21A, but thisimplementation is not limiting. A gas lead-out port 25 connected to thesynthesis apparatus 3 may be provided in the target container 21A.

The heater 22A and the heater 22B in the radioisotope producingapparatus 2A according to the present variation can be controlled asfollows. As described above, the boiling point of for instance astatine²¹¹At at normal pressure (1 atmosphere) is 337° C., and the boilingpoint of iodine ¹²⁴I at normal pressure is 184° C.; hence, it wasnecessary to adjust the temperature in the interior of the crucible 21for instance to be 337° C. or higher, in order to allow both astatine²¹¹At and iodine ¹²⁴I to evaporate in the radioisotope producingapparatus 2 of the above embodiment, and allow astatine ²¹¹At and iodine¹²⁴I to migrate from the liquid phase portion into the gas in the gasphase portion. In the radioisotope producing apparatus 2A according tothe present variation, however, a configuration is adopted in which theliquid alloy in the target container 21A is transferred to the storagecontainer 21B, and accordingly astatine ²¹¹At and iodine ¹²⁴I can beallowed to evaporate within the storage container 21B, and allowed tomigrate from the liquid phase portion into the gas in the gas phaseportion, by bringing the storage container 21B to 337° C. or above bymeans of the heater 22B. That is, the temperature in the targetcontainer 21A can be adjusted to a temperature lower than 337° C. In acase where the beam windows 26, 27 cannot withstand a temperature of337° C. or higher, the present variation allows therefore astatine ²¹¹Atand iodine ¹²⁴I to migrate into the gas in the gas phase portion, evenif the target container 21A is brought to the heat resistancetemperature of the beam windows 26, 27.

FIG. 8 is a diagram illustrating a second variation of the radioisotopeproducing apparatus. In a radiolabeled compound producing apparatus 1Aaccording to the present second variation, an alloy as a targetsubstance within the target container 21A is irradiated with a radiationbeam, to generate two or more radioisotopes in the alloy, whereupon thealloy that has given rise to the radioisotopes is transferred to thestorage container 21B, the radioisotopes migrate into a gas in thestorage container 21B, and the radioisotopes are combined with a labelprecursor in the synthesis apparatus 3.

Also in the radiolabeled compound producing apparatus 1A of the presentsecond variation, an alloy serves as the target substance, as in theradiolabeled compound producing apparatus 1 of the above embodiment.Accordingly, two or more types of objective radioisotopes can begenerated simultaneously within a liquid target, and a radiolabeledcompound that is labeled with two or more types of radioisotopes can begenerated, through irradiation of the alloy as the target substance witha same radiation beam.

In the above embodiment and the first and second variations, examples ofa radiolabeled compound have been illustrated in the form of an RI druglabeled with astatine ²¹¹At and iodine ¹²⁴I, through irradiation of analloy of bismuth Bi and antimony Sb with a radiation beam. However, theabove embodiment and variations are not limited to such animplementation. The radiolabeled compound produced in the radiolabeledcompound producing apparatus 1 may result from incorporating forinstance sulfur S, gallium Ga, selenium Se, tin Sn, tellurium Te, leadPb or the like into a target substance, to thereby generate variousradioisotopes of chlorine Cl, arsenic As, bromine Br or the like thatare then bound to a single carrier.

Second Embodiment

The radioisotope producing apparatus 2A in the above variation can beused for instance by being replaced by a crucible according to theembodiment described below.

FIG. 9 is a diagram illustrating a configuration example of aradioisotope producing apparatus of the present second embodiment. Aradioisotope producing apparatus 100 has a crucible 102, a heater 104, ajacket 106, a beam port 110, a beam window 112, a beam window 114, aninlet 122, an outlet 124 and a trap 130.

The crucible 102 is a heat-resistant container in which a substance thatconstitutes a target (for instance bismuth) is melted. The crucible 102is a storage container that stores a target-constituting substance. Forinstance, quartz, a ceramic or a metal is used as the crucible 102. Thecrucible 102 is required to be at least heat-resistant enough towithstand a temperature of the melting point of the target-constitutingsubstance. The crucible 102 is sealed, but a gas can be led into and outof the crucible 102 via the inlet 122 and the outlet 124. A beam port110 is connected to the crucible 102. The crucible 102 is an example ofa heat-resistant container.

The heater 104 is a heating means for heating the crucible 102. Theheater 104 heats the crucible 102 up, to thereby heat up thetarget-constituting substance in the crucible 102. This allows promotingmelting of the target substance. The target substance is typicallymelted and liquefied. For instance, a micro sheath heater is used as theheater 104. The heater 104 is not limited to a micro sheath heater.Further, the target-constituting substance in the crucible 102 need notliquefy entirely. That is, part of the target-constituting substance mayremain as a solid. The target-constituting substance liquefies whenheated by the heater 104. In the interior of the crucible 102, there isa liquid phase by the liquefied substance, and a gas phase from a gas orthe like that is introduced from the inlet 122. The heater 104 is anexample of a heating unit.

Herein an instance is exemplified in which a target substance is heatedby the heater 104, and the substance is liquefied, but the heating meansis not limited thereto. For instance, the rise in temperature that iselicited in a beam irradiation portion upon irradiation of the targetsubstance with a radiation beam (rise in temperature derived from heatfrom a nuclear reaction) can also be exploited herein. A combination oftwo or more conventionally known heating means can also be used, forinstance heating by the heater 104, and warming derived from irradiationwith the radiation beam.

The jacket 106 is a cooling space disposed around the crucible 102. Aninlet and an outlet for a coolant (for instance air) are provided in thejacket 106, such that the crucible 102 is cooled through introduction ofthe coolant into the jacket 106 via the inlet. Cooling can beaccomplished by discontinuing heating by the heater 104, or more quicklythrough introduction of the coolant into the jacket 106. The coolantintroduced into the jacket 106 is not limited to air (for instance airat normal temperature), and may be another gas such as nitrogen, or aliquid such as water.

And instance where the crucible 102 is cooled through introduction of acoolant into the jacket 106 is explained herein as an example of acooling method of the crucible 102, but the cooling method is notlimited thereto, and a combination of one, two or more conventionallyknown cooling means can be resorted to. For instance, an element such asa Peltier element can be used herein.

The beam port 110 is a passage for introduction of the radiation beamthat irradiates the target-constituting substance in the crucible 102.The interior of the beam port 110 is evacuated or has a gas (forinstance He gas) introduced thereinto. The beam port 110 has a tubularshape both ends of which are plugged by the beam window 112 and the beamwindow 114. The beam window 112 is connected to a radiation beamgenerator such as an accelerator. The beam window 112 and the beamwindow 114 are, for instance, metal plates. A radiation beam acceleratedby an accelerator or the like included in the radiation beam generatorenters the beam port 110 from the beam window 112, passes through thebeam window 114, and strikes into the crucible 102. The target(typically a liquefied liquid target) is irradiated in this manner. Thebeam window 112 and the beam window 114 are substances through which atleast part of the radiation beam can pass. The beam window 114 is asubstance that does not melt even at the temperature of the liquidtarget in the interior of the crucible 102. The beam port 110, the beamwindow 112 and the beam window 114 are examples of beam introductionportions.

The inlet 122 is an inlet through which a gas is introduced into thecrucible 102. The inlet 122 is for instance a tubular pipe. The inlet122 connects the interior and the exterior of the crucible 102, so thata gas can be led into/out of the crucible 102. A gas for recovery ofradioisotopes is introduced through the inlet 122. The gas which can bepreferably used includes a gas that does not liquefy or solidify throughcooling by the below-described trap 130. The above gas is for instanceHe gas. The gas is introduced through the inlet 122 and is discharged asa result from the outlet 124. In consequence, this elicits flow of gasfrom the inlet 122 towards the outlet 124, in the gas phase in thecrucible 102. As a result of such gas flow it becomes possible toconvey, towards the outlet, the radioisotopes having migrated into thegas phase. The amount of gas discharged from the outlet 124 can beadjusted through adjustment of the amount of gas introduced through theinlet 122. The pressure of the gas phase in the crucible 102 can becontrolled for instance through adjustment of the amount of gas that isintroduced, for example by adjusting the amount of gas that isdischarged from the outlet 124 (for instance by reducing the flow rateof the gate, and typically plugging the outlet 124), or by plugging thedischarge side of the trap 130. The pressure of the gas phase in thecrucible 102 can be controlled, with yet higher precision, by combiningadjustment of the amount of gas discharged from the outlet 124 oradjustment of the amount of gas discharged from the discharge side ofthe trap 130, with adjustment of amount of gas that is introducedthrough the inlet 122.

The outlet 124 is an outlet through which gas from the crucible 102 isdischarged. The outlet 124 is, for instance, a tubular pipe. The outlet124 connects the interior of the crucible 102 and the trap 130, so thata gas can be led out of the crucible 102 and into the trap 130. Forinstance, the gas introduced through the inlet 122, and vaporizedradioisotopes, are discharged from the outlet 124. The radioisotopes aresubstances generated through irradiation of a liquid target with aradiation beam.

The trap 130 is a device for separating and extracting the radioisotopefrom the gas introduced from the crucible 102. The trap 130 ishermetically connected to the crucible 102, so as to enable conveyanceof a gas containing the radioisotopes. For instance, the gas introducedfrom the crucible 102 is cooled in the trap 130. As a result, it becomespossible to separate radioisotopes from the gas (typically a mixed gaswith He) that contains the radioisotopes, through liquefaction orsolidification of the radioisotopes. The cooling is not particularlylimited as long as the radioisotopes can be separated from the gasmixture; for instance, the cooling temperature may be set to be equal toor lower than the boiling points of the radioisotopes, and preferablyequal to or lower than the melting points or equal to or lower than thefreezing points of the radioisotopes. More preferably, the coolingtemperature is set to be lower than the melting points and the freezingpoints of the radioisotopes. For instance, the cooling temperature canbe set to be 4° C. (277K) or lower, typically −10° C. (263K) or lower,preferably −80° C. (193K) or lower, and more preferably −196° C. (77K)or lower. For instance, cooling water, acetone-dry ice, liquid nitrogenor the like can be used as a cooling means. The radioisotopes can beseparated herein since He gas does not liquefy or solidify at thetemperature of liquid nitrogen (77K). The separated gas (for instance Hegas), discharged from the trap 130, may be introduced again through theinlet 122 into the crucible 102. In the trap 130 the radioisotopes canbe separated in accordance with a method similar to conventionally knowndry distillation. The trap 130 is an example of an extraction unit.

A temperature measuring means such as one or more thermocouples may bedisposed in the crucible 102. The temperature measuring means allowsmeasuring the temperature at a position of the liquid phase and thetemperature at the position of the gas phase, in the crucible 102. It isfor instance possible to determine whether the target-constitutingsubstance is liquefied or not, through measurement of the temperature ofthe liquid phase position.

Operation Example

FIG. 10 is a diagram illustrating an example of the operation flow ofthe radioisotope producing apparatus. Herein a target-constitutingsubstance is already disposed in the crucible 102. A predeterminedamount of He gas per unit time is introduced through the inlet 122.

In S101, the heater 104 of the radioisotope producing apparatus 100heats up the crucible 102. The heater 104 may be controlled for instanceby a control device, for instance by a computer or the like. Thetarget-constituting substance in the crucible 102 is heated (typically,melted to a liquid) as a result of heating of the crucible 102.Preferably, the crucible 102 is heated to a temperature at or above themelting point of the target-constituting substance. Thetarget-constituting substance having become a liquid will also bereferred to as liquid target. Herein bismuth (Bi) serves as thetarget-constituting substance. The target-constituting substance is forinstance an element of group 14, group 15 or group 16 of the periodictable. The melting point of bismuth is 271° C., and accordingly itsuffices to heat up the crucible 102 at a temperature of 271° C. orhigher. Herein the crucible 102 is set to be heated to 300° C. by theheater 104. The temperature of the target (liquid target) is preferablya temperature at which the proportion of the saturated vapor pressure ofthe respective generated radioisotope, relative to the saturated vaporpressure of the liquid target, is high. In order to efficiently obtainan objective radioisotope, it is preferable to select a respectivetarget element such that the proportion of the saturated vapor pressureof the generated radioisotope relative to the saturated vapor pressureof the liquid target is high. The type of the radiation beam to beprojected in this case is selected as described further on.

In S102, the liquid target in the crucible 102 is irradiated with aradiation beam, via the beam port 110. Examples of radiating of theradiation beam include for instance a-beams (⁴He²⁺), ³He²⁺, ¹H⁺, ²H⁺,⁷Li³⁺ and the like. Herein a-beams serve as the radiating of theradiation beam. The radiation beams utilized are ¹H⁺, ²H⁺, ⁴He²⁺, ³He²⁺or ⁷Li³⁺ in a case where target-constituting substance is an element ofgroup 13, group 14, group 15 or group 16. In consequence, the mainradioisotopes generated as a result of a nuclear reaction between thetarget-constituting substance and the radiation beam are elements ofgroup 15, group 16, group 17 and group 18. Preferably, the element ofthe target is a metal.

In S103, a radioisotope is generated as a result of a nuclear reactionbetween the target-constituting substance and the radiation beam. Thetarget-constituting substance is Bi, and the main radioisotope that isgenerated is ²¹¹At, when the radiation beam is □-beams. Within theliquid phase of the crucible 102, moreover, Bi warmed by the heat of thenuclear reaction rises up, whereas Bi cooled by the gas in the gasphase, or air or the like passing through the wall of the crucible 102,descends; convection of Bi is driven thereby. The temperature of Bi inthe liquid phase can be kept constant thereby.

In S104, the radioisotope generated through irradiating with theradiation beam evaporates. For instance, the saturated vapor pressure ofAt, at the melting point (302° C.), is 4×10⁴ Pa. The generated Atevaporates until the partial pressure of At in the crucible 102 reachesthe saturated vapor pressure. For instance, the saturated vapor pressureof Bi at the melting point (271° C.) is 1.6×10⁻⁵ Pa. The generated Bievaporates until the partial pressure of Bi in the crucible 102 reachesthe saturated vapor pressure. Assuming that the saturated vapor pressureof At, at the melting point of Bi (271° C.), is substantially the sameas the saturated vapor pressure at the melting point of At (302° C.),then the saturated vapor pressure of At is 10⁹ times or more larger thanthe saturated vapor pressure of Bi. In the liquid phase of the crucible102, therefore, most of the elements that evaporate from the liquidsurface (elements migrating from the liquid phase to the gas phase) isAt, since the partial pressure of Bi reaches immediately the saturatedvapor pressure in the gas phase, even if the proportion of At withrespect to Bi is very small. In a case for instance where thetemperature of the liquid target is 300° C., the proportion of At in theelements evaporated from the liquid surface is 99% or higher, if thevolume of Bi is appropriately set. That is, At constitutes most of theelements that evaporate from the liquid surface. The amount of Atpresent in the gas phase is much larger than the amount of Bi present inthe gas phase. Thus, At becomes separated from Bi as a result.

In a case where the saturated vapor pressure of an element generated byirradiation is high relative to the saturated vapor pressure of thetarget-constituting element, the greater part of the element evaporatedfrom the liquid surface of the liquid phase is the element(radioisotope) to be generated. The radioisotope migrates into thegenerated gas phase (into the gas) as a result of irradiation of thetarget-constituting element with a radiation beam.

FIG. 11 is a table illustrating examples of the relationship between thesaturated vapor pressure of elements in group 14, group 15, group 16 andgroup 17, and temperature. For instance, the saturated vapor pressure ofGe in group 14, at 2014° C., is 10³ Pa. It is known that in principlethe saturated vapor pressure of an element increases monotonically withtemperature. The saturated vapor pressures of elements of a same periodare compared herein. In the table of FIG. 11, a comparison betweenidentical saturated vapor pressures reveals that the temperatures in theelements of group 14, group 15 and group 16 are higher than thetemperatures in group 17. In a comparison at a same temperature, thesaturated vapor pressures of elements of group 14, group 15 and group 16are lower than the saturated vapor pressures of elements of group 17.Generally, the boiling points of elements of group 18 are very muchlower than the boiling points of other elements. In a comparison at asame temperature, therefore, the saturated vapor pressures of elementsof group 14, group 15 and group 16 are lower than the saturated vaporpressures of elements of group 18. That is, the saturated vaporpressures of the elements of group 14, group 15 and group 16, at themelting points of the elements of group 14, group 15 and group 16, arelower than the saturated vapor pressures of the elements of group 17 andgroup 18 at the melting points of the elements of group 14, group 15 andgroup 16. In other words, the elements of group 17 and group 18 aregaseous at the melting points of the elements of group 14, group 15 andgroup 16. The proportion of radioisotope with respect to the elementevaporated from the liquid surface rises through the use of an elementof group 14, group 15 or group 16 as the liquid target, and by settingan element of group 17 or group 18 as the element (radioisotope) to begenerated.

In S105 the radioisotope (for instance ²¹¹At) evaporated from the liquidsurface of the liquid phase into the gas phase passes through the outlet124 together with for instance He gas of the gas phase and reaches thetrap 130. The radioisotope is extracted in the trap 130 for instancethrough cooling using liquid nitrogen or the like. At the time ofcooling with liquid nitrogen, He gas remains as a gas, and slips throughthe trap 130, whereas the radioisotope remains in the trap 130, forinstance by solidifying. The radioisotope can be separated and extractedas a result.

In the radioisotope producing apparatus 100 the radioisotope can beseparated and extracted in the trap 130 while the radiation beam goes onbeing projected. In the radioisotope producing apparatus 100,specifically, radiating of the radiation beam and extraction of theradiation isotope can be performed in parallel. When radiating of theradiation beam and extraction of the radiation isotope are parallel,either one of the processes of radiating of the radiation beam andextraction of the radiation isotope may be discontinued. The targetelement need not be removed from the crucible 202 at the time ofextraction of the radioisotope. As a result, the radioisotope producingapparatus 100 allows generating radioisotopes efficiently.

(Variation)

FIG. 12 is a diagram illustrating a configuration example of aradioisotope producing apparatus of a variation of the present secondembodiment. A radioisotope producing apparatus 200 in FIG. 4 has acrucible 202, a heater 204, a nozzle 208, a beam port 210, a beam window212, a beam window 214, an inlet 222, an outlet 224, a trap 230, a pump240 and a heat exchanger 250. The radioisotope producing apparatus 200may have a jacket for cooling of the crucible 202, similarly to theradioisotope producing apparatus 100 in FIG. 11.

The crucible 202, the heater 204, the beam port 210, the beam window212, the beam window 214, the inlet 222, the outlet 224 and the trap 230have configurations identical to those of corresponding members of theradioisotope producing apparatus 100.

A passage for discharging a liquid target is provided at the bottom ofthe liquid phase of the crucible 202, such that a liquid target isdischarged from the crucible 202 by the action of the pump 240. Thedischarged liquid target is cooled by the heat exchanger 250. The cooledliquid target is introduced into the nozzle 208 disposed at the top inthe crucible 202. The liquid target introduced into the nozzle 208 flowsin waterfall fashion from the bottom of the nozzle 208 and reaches theliquid phase of the crucible 202. The beam port 210 is installed so thatthe liquid target flowing out of the nozzle 208 is irradiated with aradiation beam. Heat generated by nuclear reactions can be efficientlyremoved and rises in the temperature in the crucible 202 can besuppressed, through forced circulation of the liquid target.

The radioisotope producing apparatus 200 operates in the same manner asthe radioisotope producing apparatus 100, except for the portion inwhich the liquid target is forcibly caused to circulate.

(Action and Effect of the Second Embodiment)

Solid targets attached to an apparatus have conventionally beenirradiated with a radiation beam, to generate a radioisotope within thesolid target. In consequence, the solid target attached to the apparatuswas removed after irradiation, and the radioisotope was extractedthrough dry distillation of the solid target, for instance by heatingand dissolution. A time loss was thus incurred in the process fromremoval of the solid target until dry distillation was complete.Further, irradiation of a solid target necessitated herein curtailmentof the irradiation output, so as to preclude melting of the solidtarget. Curtailing thus the output entails a reduction in the amount ofgenerated radioisotope.

In the apparatus of the present second embodiment, by contrast, a liquidtarget is irradiated with a radiation beam, to generate a radioisotopewithin the liquid target. The proportion of the generated radioisotopethat evaporates, relative to the element that evaporates from the liquidphase, can be increased through proper adjustment of temperature andpressure in the vicinity of the liquid surface of the liquid target. Inthe above example, the saturated vapor pressure of ²¹¹At is much higherthan the saturated vapor pressure of Bi, and hence ²¹¹At makes up mostof the elements that evaporate from the liquid phase. Accordingly, theradioisotope is purified through recovery of the evaporated element. Theprocess of generation, separation, and purification of the radioisotopeproceeds spontaneously until the partial pressure of ²¹¹At in thevicinity of the liquid surface of the liquid target reaches a saturatedvapor pressure and an equilibrium state is attained. Therefore, ²¹¹Atcan go on being produced, continuously or intermittently, if At isextracted continuously or at appropriate timings. In the apparatus ofthe present second embodiment the radioisotope can be extracted withoutdiscontinuation of irradiating of the liquid target with the radiationbeam, and without removal of the liquid target, and hence producing ofthe radioisotope, from generation up to extraction, can be accomplishedin a shorter time. That is, the apparatus of the present secondembodiment allows extracting a radiation isotope from a gas thatcontains an evaporated radiation isotope generated through irradiationwith a radiation beam.

In the apparatus of the present second embodiment the target is aliquid, and accordingly it is not necessary to suppress the output ofirradiation so as to preclude melting of the target, and the irradiationoutput of the radiation beam can be kept large, without rises in thetemperature of the liquid target, through cooling of the liquid targetfor instance by convection or forced circulation. A greater amount ofradioisotope can be produced by increasing the irradiation output.

Examples have been explained, in the above embodiments and variations,of an instance where bismuth (Bi) is used as the target substance anda-beams are used as the radiation beam that irradiates the targetsubstance, to thereby generate ²¹¹At as a radioisotope. In the aboveembodiments and variations, however, a metal other than bismuth (Bi) maybe used as the target substance, a radiation beam other than a-beams maybe used to irradiate the target substance, and a radioisotope other than²¹¹At may be generated.

The tables below set out combination patterns of target substances,radiation beams and radioisotopes that can be used in the aboveembodiments and variations.

TABLE 1 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER  1 16 S 34 p, n 17 Cl  34m  2 16 S 34 α, n 18 Ar 37  3 31 Ga 69 α, n 33 As 72  4 31 Ga 69 α, 2n33 As 71  5 31 Ga 69 α, 3n 33 As 70  6 31 Ga 69 7Li, d 33 As 74  7 31 Ga71 α, n 33 As 74  3 31 Ga 71 α, 2n 33 As 73  9 31 Ga 71 α, 3n 33 As 7210 31 Ga 71 7Li, p 33 As 77 11 31 Ga 71 7Li, d 33 As 76 12 34 Se 74 p, n35 Br 74 13 34 Se 74 α, n 36 Kr 77 14 34 Se 74 α, 2n 36 Kr 76 15 34 Se74 α, 3n 36 Kr 75 16 34 Se 76 p, n 35 Br 76 17 34 Se 76 p, 2n 35 Br 7518 34 Se 76 p, 3n 35 Br 74 19 34 Se 76 α, n 36 Kr 79 20 34 Se 76 α, 3n36 Kr 77 21 34 Se 77 p, n 35 Br 77 22 34 Se 77 p, 2n 35 Br 76 23 34 Se77 p, 3n 35 Br 75 24 34 Se 77 α, 2n 36 Kr 79 25 34 Se 78 p, 2n 35 Br 7726 34 Se 78 p, 3n 35 Br 76 27 34 Se 78 α, 3n 36 Kr 79 28 34 Se 80 p, n35 Br 80 29 34 Se 80 p, n 35 Br  80 m 30 34 Se 80 p, 3n 35 Br 78DESCENDANT HEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No. HALF-LIFE 12 TARGET PRODUCT TARGET PRODUCT  1 31.99 m Liq. Gas Gas Gas  2 35.01 dLiq. Gas Gas Gas  3 26.0 h Liq. Sol. Liq. Gas  4 65.30 h Ge-71 Liq. Sol.Liq. Gas  5 52.6 m Liq. Sol. Liq. Gas  6 17.77 d Liq. Sol. Liq. Gas  717.77 d Liq. Sol. Liq. Gas  3 80.30 d Liq. Sol. Liq. Gas  9 26.0 h Liq.Sol. Liq. Gas 10 38.79 h Liq. Sol. Liq. Gas 11 26.24 h Liq. Sol. Liq.Gas 12 25.4 m Liq. Gas Liq. Gas 13 74.4 m Br-77 Liq. Gas Liq. Gas 1414.8 h Br-76 Liq. Gas Liq. Gas 15  4.60 m Br-75 Se-75 Liq. Gas Liq. Gas16 16.1 h Liq. Gas Liq. Gas 17 96.7 m Se-75 Liq. Gas Liq. Gas 18 25.4 mLiq. Gas Liq. Gas 19 35.04 h Liq. Gas Liq. Gas 20 74.4 m Br-77 Liq. GasLiq. Gas 21 57.04 h Liq. Gas Liq. Gas 22 16.1 h Liq. Gas Liq. Gas 2396.7 m Se-75 Liq. Gas Liq. Gas 24 35.04 h Liq. Gas Liq. Gas 25 57.04 hLiq. Gas Liq. Gas 26 16.1 h Liq. Gas Liq. Gas 27 35.04 h Liq. Gas Liq.Gas 28 17.68 m Liq. Gas Liq. Gas 29  4.42 h Liq. Gas Liq. Gas 30  6.45 mLiq. Gas Liq. Gas

TABLE 2 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER 31 34 Se  80 α, n 36 Kr  83 m 32 34 Se  82 p, n 35 Br  82 33 34 Se  82 p, 3n 35 Br  80 34 34 Se 82 p, 3n 35 Br   80 m 35 34 Se  82 α, n 36 Kr  85 36 50 Sn 112 7Li, 3n53 I 116 37 50 Sn 112 7Li, 4n 53 I 115 38 50 Sn 112 7Li, 5n 53 I 114 3950 Sn 112 7Li, 6n 53 I 113 40 50 Sn 112 7Li, 7n 53 I 112 41 50 Sn 1127Li, 8n 53 I 111 42 50 Sn 112 7Li, 9n 53 I 110 43 50 Sn 114 7Li, 3n 53 I118 44 50 Sn 114 7Li, 4n 53 I 117 45 50 Sn 114 7Li, 5n 53 I 116 46 50 Sn114 7Li, 6n 53 I 115 47 50 Sn 114 7Li, 7n 53 I 114 48 50 Sn 114 7Li, 8n53 I 113 49 50 Sn 114 7Li, 9n 53 I 112 50 50 Sn 114 7Li, 6Li 53 I 115 5150 Sn 115 7Li, 3n 53 I 119 52 50 Sn 115 7Li, 4n 53 I 118 53 50 Sn 1157Li, 5n 53 I 117 54 50 Sn 115 7Li, 6n 53 I 116 55 50 Sn 115 7Li, 7n 53 I115 56 50 Sn 115 7Li, 8n 53 I 114 57 50 Sn 115 7Li, 9n 53 I 113 58 50 Sn116 7Li, 3n 53 I 120 59 50 Sn 116 7Li, 3n 53 I  120 m 60 50 Sn 116 7Li,4n 53 I 119 DESCENDANT HEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No.HALF-LIFE 1 2 TARGET PRODUCT TARGET PRODUCT 31  1.83 h Liq. Gas Liq. Gas32  35.3 h Liq. Gas Liq. Gas 33  17.68 m Liq. Gas Liq. Gas 34  4.42 hLiq. Gas Liq. Gas 35  10.74 y Liq. Gas Liq. Gas 36  2.91 s Te-116 Sb-116Liq. Gas Liq. Gas 37  1.3 m Te-115 Sb-115 Liq. Gas Liq. Gas 38  2.1 sTe-114 Sb-114 Liq. Gas Liq. Gas 39  6.6 s Te-113 Sb-113 Liq. Gas Liq.Gas 40  3.34 s Te-112 Sb-112 Liq. Gas Liq. Gas 41  2.5 s Te-111 Sb-111Liq. Gas Liq. Gas 42 664 ms Te-110 Sb-110 Liq. Gas Liq. Gas 43  13.7 mTe-118 Liq. Gas Liq. Gas 44  2.22 m Te-117 Sb-117 Liq. Gas Liq. Gas 45 2.91 s Te-116 Sb-116 Liq. Gas Liq. Gas 46  1.3 m Te-115 Sb-115 Liq. GasLiq. Gas 47  2.1 s Te-114 Sb-114 Liq. Gas Liq. Gas 48  6.6 s Te-113Sb-113 Liq. Gas Liq. Gas 49  3.34 s Te-112 Sb-112 Liq. Gas Liq. Gas 50 1.3 m Te-115 Sb-115 Liq. Gas Liq. Gas 51  19.1 m Te-119 Sb-119 Liq. GasLiq. Gas 52  13.7 m Te-118 Liq. Gas Liq. Gas 53  2.22 m Te-117 Sb-117Liq. Gas Liq. Gas 54  2.91 s Te-116 Sb-116 Liq. Gas Liq. Gas 55  1.3 mTe-115 Sb-115 Liq. Gas Liq. Gas 56  2.1 s Te-114 Sb-114 Liq. Gas Liq.Gas 57  6.6 s Te-113 Sb-113 Liq. Gas Liq. Gas 58  81.6 m Sb-120 Liq. GasLiq. Gas 59  53 m Sb-120 Liq. Gas Liq. Gas 60  19.1 m Te-119 Sb-119 Liq.Gas Liq. Gas

TABLE 3 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER 61 50 Sn 116 7Li, 5n 53 I118 62 50 Sn 116 7Li, 6n 53 I 117 63 50 Sn 116 7Li, 7n 53 I 116 64 50 Sn116 7Li, 8n 53 I 115 65 50 Sn 116 7Li, 9n 53 I 114 66 50 Sn 117 7Li, 3n53 I 121 67 50 Sn 117 7Li, 4n 53 I 120 68 50 Sn 117 7Li, 4n 53 I  120 m69 50 Sn 117 7Li, 5n 53 I 119 70 50 Sn 117 7Li, 6n 53 I 118 71 50 Sn 1177Li, 7n 53 I 117 72 50 Sn 117 7Li, 8n 53 I 116 73 50 Sn 117 7Li, 9n 53 I115 74 50 Sn 118 7Li, 4n 53 I 121 75 50 Sn 118 7Li, 5n 53 I 120 76 50 Sn118 7Li, 5n 53 I  120 m 77 50 Sn 113 7Li, 6n 53 I 119 78 50 Sn 113 7Li,7n 53 I 118 79 50 Sn 118 7Li, 8n 53 I 117 80 50 Sn 118 7Li, 9n 53 I 11681 50 Sn 119 7Li, 3n 53 I 123 82 50 Sn 119 7Li, 5n 53 I 121 83 50 Sn 1197Li, 6n 53 I 120 84 50 Sn 119 7Li, 6n 53 I  120 m 85 50 Sn 119 7Li,7n 53I 119 86 50 Sn 119 7Li, 8n 53 I 118 87 50 Sn 119 7Li, 9n 53 I 117 88 50Sn 120 7Li, 3n 53 I 124 89 50 Sn 120 7Li, 4n 53 I 123 90 50 Sn 120 7Li,6n 53 I 121 DESCENDANT HEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No.HALF-LIFE 1 2 TARGET PRODUCT TARGET PRODUCT 61 13.7 m Te-118 Liq. GasLiq. Gas 62  2.22 m Te-117 Sb-117 Liq. Gas Liq. Gas 63  2.91 s Te-116Sb-116 Liq. Gas Liq. Gas 64  1.3 m Te-115 Sb-115 Liq. Gas Liq. Gas 65 2.1 s Te-114 Sb-114 Liq. Gas Liq. Gas 66  2.12 h Te-121 Liq. Gas Liq.Gas 67 81.6 m Sb-120 Liq. Gas Liq. Gas 68 53 m Sb-120 Liq. Gas Liq. Gas69 19.1 m Te-119 Sb-119 Liq. Gas Liq. Gas 70 13.7 m Te-118 Liq. Gas Liq.Gas 71  2.22 m Te-117 Sb-117 Liq. Gas Liq. Gas 72  2.91 s Te-116 Sb-116Liq. Gas Liq. Gas 73  1.3 m Te-115 Sb-115 Liq. Gas Liq. Gas 74  2.12 hTe-121 Liq. Gas Liq. Gas 75 81.6 m Sb-120 Liq. Gas Liq. Gas 76 53 mSb-120 Liq. Gas Liq. Gas 77 19.1 m Te-119 Sb-119 Liq. Gas Liq. Gas 7813.7 m Te-118 Liq. Gas Liq. Gas 79  2.22 m Te-117 Sb-117 Liq. Gas Liq.Gas 80  2.91 s Te-116 Sb-116 Liq. Gas Liq. Gas 81 13.22 h Liq. Gas Liq.Gas 82  2.12 h Te-121 Liq. Gas Liq. Gas 83 81.6 m Sb-120 Liq. Gas Liq.Gas 84 53 m Sb-120 Liq. Gas Liq. Gas 85 19.1 m Te-119 Sb-119 Liq. GasLiq. Gas 86 13.7 m Te-118 Liq. Gas Liq. Gas 87  2.22 m Te-117 Sb-117Liq. Gas Liq. Gas 88  4.17 d Liq. Gas Liq. Gas 89 13.22 h Liq. Gas Liq.Gas 90  2.12 h Te-121 Liq. Gas Liq. Gas

TABLE 4 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER  91 50 Sn 120 7Li, 7n 53 I120  92 50 Sn 120 7Li, 7n 53 I  120 m  93 50 Sn 120 7Li, 8n 53 I 119  9450 Sn 120 7Li, 9n 53 I 118  95 50 Sn 122 7Li, 3n 53 I 126  96 50 Sn 1227Li, 4n 53 I 125  97 50 Sn 122 7Li, 5n 53 I 124  98 50 Sn 122 7Li, 6n 53I 123  99 50 Sn 122 7Li, 8n 53 I 121 100 50 Sn 122 7Li, 9n 53 I 120 10150 Sn 122 7Li, 9n 53 I  120 m 102 51 Sb 121 α, n 53 I 124 103 51 Sb 121α, 2n 53 I 123 104 51 Sb 121 7Li, 3n 54 Xe 125 105 51 Sb 121 7Li, 5n 54Xe 123 106 51 Sb 121 7Li, 6n 54 Xe 122 107 51 Sb 121 7Li, 7n 54 Xe 121108 51 Sb 121 7Li, 8n 54 Xe 120 109 51 Sb 121 7Li, d 53 I 126 110 51 Sb123 α, n 53 I 126 111 51 Sb 123 α, 2n 53 I 125 112 51 Sb 123 α, 3n 53 I124 113 51 Sb 123 7Li, 3n 54 Xe 127 114 51 Sb 123 7Li, 5n 54 Xe 125 11551 Sb 123 7Li, 7n 54 Xe 123 116 51 Sb 123 7Li, 8n 54 Xe 122 117 51 Sb123 7Li, 9n 54 Xe 121 118 51 Sb 123 7Li, p 53 I 129 119 51 Sb 123 7Li, d53 I 128 120 52 Te 120 p, n 53 I 120 DESCENDANT HEATING TEMPERATURENUCLIDE(S) 350 oC 650 oC No. HALF-LIFE 1 2 TARGET PRODUCT TARGET PRODUCT 91 81.6 m Sb-120 Liq. Gas Liq. Gas  92 53 m Sb-120 Liq. Gas Liq. Gas 93 19.1 rn Te-119 Sb-119 Liq. Gas Liq. Gas  94 13.7 m Te-118 Liq. GasLiq. Gas  95 12.93 d Liq. Gas Liq. Gas  96 59.4 d Liq. Gas Liq. Gas  97 4.17 d Liq. Gas Liq. Gas  98 13.22 h Liq. Gas Liq. Gas  99  2.12 hTe-121 Liq. Gas Liq. Gas 100 81.6 m Sb-120 Liq. Gas Liq. Gas 101 53 mSb-120 Liq. Gas Liq. Gas 102  4.17 d Sol. Gas Liq. Gas 103 13.22 h Sol.Gas Liq. Gas 104 16.9 h Sol. Gas Liq. Gas 105  2.08 h Sol. Gas Liq. Gas106 20.1 h Sol. Gas Liq. Gas 107 40.1 m Sol. Gas Liq. Gas 108 40 m Sol.Gas Liq. Gas 109 12.93 d Sol. Gas Liq. Gas 110 12.93 d Sol. Gas Liq. Gas111 59.4 d Sol. Gas Liq. Gas 112  4.17 d Sol. Gas Liq. Gas 113 36.4 dSol. Gas Liq. Gas 114 16.9 h Sol. Gas Liq. Gas 115  2.08 h Sol. Gas Liq.Gas 116 20.1 h Sol. Gas Liq. Gas 117 40.1 m Sol. Gas Liq. Gas 118 1.57e7 y Sol. Gas Liq. Gas 119 25.0 m Sol. Gas Liq. Gas 120 81.6 mSb-120 Sol. Gas Liq. Gas

TABLE 5 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER 121 52 Te 120 p, n 53 I 120 m 122 52 Te 120 p, 2n 53 I 119 123 52 Te 120 p, 3n 53 I 118 124 52Te 120 α, n 54 Xe 123 125 52 Te 120 α, 2n 54 Xe 122 126 52 Te 120 α, 3n54 Xe 121 127 52 Te 122 p, 2n 53 I 121 128 52 Te 122 p, 3n 53 I 120 12952 Te 122 p, 3n 53 I  120 m 130 52 Te 122 α, n 54 Xe 125 131 52 Te 122α, 3n 54 Xe 123 132 52 Te 124 p, n 53 I 124 133 52 Te 124 p, 2n 53 I 123134 52 Te 124 α, n 54 Xe 127 135 52 Te 124 α, 3n 54 Xe 125 136 52 Te 125p, n 53 I 125 137 52 Te 125 p, 2n 53 I 124 138 52 Te 125 p, 3n 53 I 123139 52 Te 125 α, 2n 54 Xe 127 140 52 Te 126 p, n 53 I 126 141 52 Te 126p, 2n 53 I 125 142 52 Te 126 p, 3n 53 I 124 143 52 Te 126 α, n 54 Xe 129 m 144 52 Te 126 α, 3n 54 Xe 127 145 52 Te 128 p, n 53 I 128 146 52Te 128 p, 3n 53 I 126 147 52 Te 128 α, n 54 Xe  131 m 148 52 Te 128 α,3n 54 Xe  129 m 149 52 Te 130 p, n 53 I 130 150 52 Te 130 p, 2n 53 I 129DESCENDANT HEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No. HALF-LIFE 12 TARGET PRODUCT TARGET PRODUCT 121 53 m Sb-120 Sol. Gas Liq. Gas 12219.1 m Te-119 Sb-119 Sol. Gas Liq. Gas 123 13.7 m Te-118 Sol. Gas Liq.Gas 124  2.08 h Sol. Gas Liq. Gas 125 20.1 h Sol. Gas Liq. Gas 126 40.1m Sol. Gas Liq. Gas 127  2.12 h Te-121 Sol. Gas Liq. Gas 128 81.6 mSb-120 Sol. Gas Liq. Gas 129 53 m Sb-120 Sol. Gas Liq. Gas 130 16.9 hSol. Gas Liq. Gas 131  2.08 h Sol. Gas Liq. Gas 132  4.17 d Sol. GasLiq. Gas 133 13.22 h Sol. Gas Liq. Gas 134 36.4 d Sol. Gas Liq. Gas 13516.9 h Sol. Gas Liq. Gas 136 59.4 d Sol. Gas Liq. Gas 137  4.17 d Sol.Gas Liq. Gas 138 13.22 h Sol. Gas Liq. Gas 139 36.4 d Sol. Gas Liq. Gas140 12.93 d Sol. Gas Liq. Gas 141 59.4 d Sol. Gas Liq. Gas 142  4.17 dSol. Gas Liq. Gas 143  8.88 d Sol. Gas Liq. Gas 144 36.4 d Sol. Gas Liq.Gas 145 25.0 m Sol. Gas Liq. Gas 146 12.93 d Sol. Gas Liq. Gas 147 11.84d Sol. Gas Liq. Gas 148  8.88 d Sol. Gas Liq. Gas 149 12.36 h Sol. GasLiq. Gas 150  1.57e7 y Sol. Gas Liq. Gas

TABLE 6 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER 151 52 Te 130 p, 3n 53 I128 152 52 Te 130 α, n 54 Xe 133 153 52 Te 130 α, n 54 Xe  133 m 154 82Pb 204 7Li, 3n 85 At 208 155 82 Pb 204 7Li, 4n 85 At 207 156 82 Pb 2047Li, 5n 85 At 206 157 82 Pb 204 7Li, 6n 85 At 205 153 82 Pb 204 7Li, 7n85 At 204 159 82 Pb 204 7Li, 8n 85 At 203 160 82 Pb 204 7Li, p 84 Po 210161 82 Pb 204 7Li, d 84 Po 209 162 82 Pb 206 7Li, 3n 85 At 210 163 82 Pb206 7Li, 4n 85 At 209 164 82 Pb 206 7Li, 5n 85 At 208 165 82 Pb 206 7Li,6n 85 At 207 166 82 Pb 206 7Li, 7n 85 At 206 167 82 Pb 206 7Li, 8n 85 At205 168 82 Pb 206 7Li, 9n 85 At 204 169 82 Pb 207 7Li, 3n 85 At 211 17082 Pb 207 7Li, 4n 85 At 210 171 82 Pb 207 7Li, 5n 85 At 209 172 82 Pb207 7Li, 6n 85 At 208 173 82 Pb 207 7Li, 7n 85 At 207 174 82 Pb 207 7Li,8n 85 At 206 175 82 Pb 207 7Li, 9n 85 At 205 176 82 Pb 208 7Li, 4n 85 At211 177 82 Pb 208 7Li, 5n 85 At 210 178 82 Pb 208 7Li, 6n 85 At 209 17982 Pb 208 7Li, 7n 85 At 208 18 0 82 Pb 208 7Li, 8n 85 At 207 DESCENDANTHEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No. HALF-LIFE 1 2 TARGETPRODUCT TARGET PRODUCT 151  25.0 m Sol. Gas Liq. Gas 152  5.25 d Sol.Gas Liq. Gas 153  2.2 d Sol. Gas Liq. Gas 154  1.63 h * Liq. Gas Liq.Gas 155  1.81 h * Liq. Gas Liq. Gas 156  30.6 m * Liq. Gas Liq. Gas 157 26.9 m * Liq. Gas Liq. Gas 153  9.12 m * Liq. Gas Liq. Gas 159  7.4 m *Liq. Gas Liq. Gas 160 138.4 d * Liq. Gas Liq. Gas 161 124 y * Liq. GasLiq. Gas 162  8.1 h * Liq. Gas Liq. Gas 163  5.42 h * Liq. Gas Liq. Gas164  1.63 h * Liq. Gas Liq. Gas 165  1.81 h * Liq. Gas Liq. Gas 166 30.6 m * Liq. Gas Liq. Gas 167  26.9 m * Liq. Gas Liq. Gas 168  9.12m * Liq. Gas Liq. Gas 169  7.214 h * Liq. Gas Liq. Gas 170  8.1 h * Liq.Gas Liq. Gas 171  5.42 h * Liq. Gas Liq. Gas 172  1.63 h * Liq. Gas Liq.Gas 173  1.81 h * Liq. Gas Liq. Gas 174  30.6 m * Liq. Gas Liq. Gas 175 26.9 m * Liq. Gas Liq. Gas 176  7.214 h * Liq. Gas Liq. Gas 177  8.1h * Liq. Gas Liq. Gas 178  5.42 h * Liq. Gas Liq. Gas 179  1.63 h * Liq.Gas Liq. Gas 180  1.81 h * Liq. Gas Liq. Gas

TABLE 7 TARGET PRODUCT ATOMIC MASS NUCLEAR ATOMIC MASS No. NUMBERELEMENT NUMBER REACTION NUMBER ELEMENT NUMBER 181 82 Pb 208 7Li, 9n 85At 206 182 83 Bi 209 α, 2n 85 At 211 133 83 Bi 209 α, 3n 85 At 210 18483 Bi 209 7Li, 3n 86 Rn 213 185 83 Bi 209 7Li, 4n 86 Rn 212 186 83 Bi209 7Li, 5n 86 Rn 211 187 83 Bi 209 7Li, 6n 86 Rn 210 188 83 Bi 209 7Li,7n 86 Rn 209 189 83 Bi 209 7Li, 8n 86 Rn 208 190 83 Bi 209 7Li, 9n 86 Rn207 DESCENDANT HEATING TEMPERATURE NUCLIDE(S) 350 oC 650 oC No.HALF-LIFE 1 2 TARGET PRODUCT TARGET PRODUCT 181 30.6 m * Liq. Gas Liq.Gas 182  7.214 h * Liq. Gas Liq. Gas 133  8.1 h * Liq. Gas Liq. Gas 18419.5 ms * Liq. Gas Liq. Gas 185 23.9 m * Liq. Gas Liq. Gas 186 14.6 h *Liq. Gas Liq. Gas 187  2.4 h * Liq. Gas Liq. Gas 188 28.8 m * Liq. GasLiq. Gas 189 24.3 m * Liq. Gas Liq. Gas 190  9.25 m * Liq. Gas Liq. Gas

The description in the column notated as “Target” in the above tablesexemplifies elements that can be used as a target substance in the aboveembodiments and variations; as set out in the tables, the elements maybe for instance sulfur (S), gallium (Ga), selenium (Se), tin (Sn),antimony (Sb), tellurium (Te), lead (Pb) and bismuth (Bi).

The description in the column notated as “nuclear reaction” in the abovetables exemplifies the types of nuclear reaction elicited by theradiation beam that irradiates the target substance, in the aboveembodiments and variations; as set out in the tables, the nuclearreaction may be for instance an a-reaction using a-particles, a preaction using protons, and a nuclear reaction using lithium. In thecolumn of nuclear reaction, the descriptor to the left of the commarepresents the particle that strikes the target substance, and thedescriptor to the right of the comma represents the particle emitted bythe target substance.

The description in the column “Progeny nuclide” in the tables denotesthe nuclide that is generated through product decay. As set out in thetables, examples of progeny nuclides include germanium (Ge) and bromine(Br). Instances where a variety of progeny nuclides are generated thatdo not fit into the column of the tables are marked with an asterisk(*).

The descriptions in the column “Target” and column “Product” of thecolumn notated as “Heating temperature” denote the state of therespective substance. The caption “Sol” denotes a solid state, “Liq”denotes a liquid state, and “Gas” denotes a gaseous state.

Various radioisotopes can be generated in the above embodiments andvariations, as set out in the column “Product” of the tables, byutilizing the combinations of target and nuclear reaction given in thetables. In the above tables, the target denotes a substance thetemperature of which, at the time of vaporization at the pressure uponirradiation with the radiation beam, is higher than the temperature atwhich the radioisotope, as the product, vaporizes under that samepressure. In the above embodiments and variations, therefore, aradioisotope can vaporize, without vaporization of the target substance,and can be extracted from the gas in the trap 130, by adjusting thetemperature of the target substance so as to lie in a temperature rangethat is equal to or higher than the temperature at the time ofvaporization of the radioisotope, under a same pressure, and that islower than the temperature at the time of vaporization of the targetsubstance under that same pressure. The term “vaporization” in thepresent application signifies that a substance that has reached agaseous state and encompasses conceptually for instance a stateresulting from transition to a gas phase by going beyond the boilingpoint or the sublimation point of that substance. Accordingly, thewording “temperature at the time of vaporization of a target substance,under a same pressure” can be rephrased as “boiling point or sublimationpoint at which a target substance evaporates, under a same pressure”.

For instance in the combination No. 1 in the tables, the boiling pointat normal pressure of sulfur (S) which is the target substance is about444° C., whereas the boiling point at normal pressure of chlorine (CI)which is the product is about −34° C., lower than that of sulfur (S).Accordingly, if the target is irradiated with a radiation beam in astate where the temperature in the crucible 102 is 350° C., as indicatedin the column “Heating temperature” of the tables, then sulfur (S) whichis the target substance remains in a liquid state, while only chlorine(CI) which is the product evaporates in the crucible 102, the chlorine(CI) having evaporated in the crucible 102 being then condensed in thetrap 130, to be extracted as a result.

For instance in the combinations No. 3 and No. 7 in the tables, theboiling point at normal pressure of gallium (Ga) which is the targetsubstance is about 2400° C., whereas the boiling point at normalpressure of arsenic (As) which is the product is about 613° C., lowerthan that of gallium (Ga). Accordingly, if the target is irradiated witha radiation beam in a state where the temperature in the crucible 102 is650° C., as indicated in the column “Heating temperature” of the tables,then gallium (Ga) which is the target substance remains in a liquidstate, while only arsenic (As) which is the product evaporates in thecrucible 102, the arsenic (As) having evaporated in the crucible 102being then condensed in the trap 130, to be extracted as a result.

For instance in the combinations No. 12, No. 16 and No. 22 in thetables, the boiling point at normal pressure of selenium (Se) which isthe target substance is about 684° C., whereas the boiling point atnormal pressure of bromine (Br) which is the product is about 58° C.,lower than that of selenium (Se). Accordingly if the target isirradiated with a radiation beam in a state where the temperature in thecrucible 102 is 350° C. or 650° C., as indicated in the column “Heatingtemperature” of the tables, then selenium (Se) which is the targetsubstance remains in a liquid state, while only bromine (Br) which isthe product evaporates in the crucible 102, the bromine (Br) havingevaporated in the crucible 102 being then condensed in the trap 130, tobe extracted as a result.

For instance in the combinations No. 102 and No. 112 in the tables, theboiling point at normal pressure of antimony (Sb) which is the targetsubstance is about 1587° C., whereas the boiling point at normalpressure of iodine (I) which is the product is about 148° C., lower thanthat of antimony (Sb). Accordingly, if the target is irradiated with aradiation beam is in a state where the temperature in the crucible 102is 350° C. or 650° C., as indicated in the column “Heating temperature”of the tables, then antimony (Sb) which is the target substance remainsin a solid or liquid state, while only iodine (I) which is the productevaporates in the crucible 102, the iodine (I) having evaporated in thecrucible 102 being then condensed in the trap 130, to be extracted as aresult.

For instance in the combination No. 186 in the tables, the boiling pointat normal pressure of bismuth (Bi) which is the target substance isabout 1564° C., whereas the boiling point at normal pressure of radon(Rn) which is the product is about −62° C., lower than that of bismuth(Bi). Accordingly if the target is irradiated with a radiation beam in astate where the temperature in the crucible 102 is 350° C. or 650° C.,as indicated in the column “Heating temperature” of the tables, thenbismuth (Bi) which is the target substance remains in a solid or liquidstate, while only radon (Rn) which is the product evaporates in thecrucible 102, the radon (Rn) having evaporated in the crucible 102 beingthen condensed in the trap 130, to be extracted as a result.

In the column “Heating temperature” of the tables, two instances, oftemperature of 350° C. and 650° C. are illustrated. However, thetemperature in the crucible 102, when a combination of target andnuclear reaction set out in the above tables is to be implemented in theabove embodiments and variations, is not limited to either 350° C. or650° C. The temperature of the target substance in the crucible 102, ina case where a combination of target and nuclear reaction set out in thetables above and to be implemented in the above embodiments andvariations, is set to an arbitrary temperature within a temperaturerange that is equal to or higher than the temperature at the time ofvaporization of the product under the pressure in the crucible 102 andthat is lower than the temperature at the time of vaporization of thetarget substance under that same pressure. For instance in thecombination No. 1 in the tables, the boiling point at normal pressure ofsulfur (S) which is the target substance is about 444° C., whereas theboiling point at normal pressure of chlorine (CI) which is the productis about −34° C., lower than that of sulfur (S). Accordingly, assumingthat the interior of the crucible 102 is at normal pressure, if thetemperature of sulfur (S) in the crucible 102 lies in the range fromabout −30° C. to about 440° C. then just chlorine (CI), which is theproduct, can be allowed to evaporate in the crucible 102, withoutvaporization of sulfur (S) which is the target substance, whereupon thechlorine (CI) having evaporated in the crucible 102 can be extracted bybeing condensed in the trap 130.

The column “Target” in the above tables sets out only the name of thetarget-constituting element, but two or more types of target substancemay be held in the crucible 102, or a substance other than a target maybe present, along with the target substance, in the crucible 102,provided that a substance serving as a target, such as those in thecolumn “Target” of the tables, is contained in the crucible 102.

In a case where an alloy is formed in the crucible 102 by charging twoor more types of substance together, the melting point is different fromthat in a case where respective substance is present alone in thecrucible 102. For instance, the melting point of an alloy produced at a58:42 ratio of bismuth (Bi) and tin (Sn), at normal pressure, is 138° C.i.e. lower than 271° C., which is the melting point of bismuth (Bi), andlower than 232° C., which is the melting point of tin (Sn). However, theboiling point itself of a product obtained by irradiating bismuth (Bi)with a radiation beam and the boiling point itself of a product obtainedby irradiating tin (Sn) with a radiation beam are unrelated, regardlessof whether the foregoing are in an alloyed state or not, and accordinglythe products can be extracted selectively in the trap 130, throughadjustment of the interior of the crucible 102 to an appropriatetemperature.

The above products can be used for diagnosis and treatment in medicine,and also in various applications other than medical purposes, such asquality management of agricultural products and industrial products. Forinstance, the above product can play a role as a tracer for observingthe state, of a plant, resulting from migration of substances from acrop soil, or a role as a reagent for verifying a surface treatmentstate in an industrial product.

REFERENCE SIGNS LIST

-   -   1, 1A Radiolabeled compound producing apparatus    -   2, 2A Radioisotope producing apparatus    -   3 Synthesis apparatus    -   21 Crucible    -   21A Target container    -   21B Storage container    -   22, 22A, 22B Heater    -   23 Beam port    -   24 Gas introduction port    -   25 Gas lead-out port    -   26 Beam window    -   27 Beam window    -   28 Jacket    -   29 Transfer pipe    -   31 First column    -   32 Second column    -   100 Radioisotope producing apparatus    -   102 Crucible    -   104 Heater    -   106 Jacket    -   110 Beam port    -   112 Beam window    -   114 Beam window    -   122 Inlet    -   124 Outlet    -   130 Trap    -   200 Radioisotope producing apparatus    -   202 Crucible    -   204 Heater    -   208 Nozzle    -   210 Beam port    -   212 Beam window    -   214 Beam window    -   222 Inlet    -   224 Outlet    -   230 Trap    -   240 Pump    -   250 Heat exchanger

1. A method for producing a radiolabeled compound, comprising the steps of: irradiating an alloy as a target substance with a radiation beam, to generate two or more radioisotopes from the alloy, and allowing the two or more radioisotopes to migrate into a gas; generating an intermediate label by allowing a first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; and generating a final label by allowing a second radioisotope different from the first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with the intermediate label.
 2. A method for producing a radiolabeled compound, comprising the steps of: irradiating an alloy of a target substance with a radiation beam, to generate two or more radioisotopes from the alloy, and allowing the two or more radioisotopes to migrate into a gas; generating a first intermediate label by allowing a first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; generating a second intermediate label by allowing a second radioisotope different from the first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; and generating a final label by condensing the first intermediate label and the second intermediate label.
 3. The method for producing a radiolabeled compound of claim 1, further comprising: a step of adjusting the temperature of the alloy so as to be a temperature at which both the first radioisotope and the second radioisotope evaporate, during irradiation with the radiation beam.
 4. An apparatus for producing a radiolabeled compound, comprising: isotope generation means for irradiating an alloy as a target substance with a radiation beam, to generate two or more radioisotopes from the alloy, and allowing the two or more radioisotopes to migrate into a gas; a first generating unit which generates an intermediate label by allowing a first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; and a second generating unit which generates a final label by allowing a second radioisotope different from the first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with the intermediate label.
 5. An apparatus for producing a radiolabeled compound, comprising: isotope generation means for irradiating an alloy as a target substance with a radiation beam, to generate two or more radioisotopes from the alloy, and allowing the two or more radioisotopes to migrate into a gas; a third generating unit which generates a first intermediate label by allowing a first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; a fourth generating unit which generates a second intermediate label by allowing a second radioisotope different from the first radioisotope, from among the two or more radioisotopes having migrated into the gas, to react with a label precursor; and a fifth generating unit which generates a final label through condensation of the first intermediate label and the second intermediate label. 6.-8. (canceled)
 9. The method for producing a radiolabeled compound of claim 2, further comprising: a step of adjusting the temperature of the alloy so as to be a temperature at which both the first radioisotope and the second radioisotope evaporate, during irradiation with the radiation beam. 